Biocompatible extremely fine tantalum filament scaffolding for bone and soft tissue prosthesis

ABSTRACT

A tissue implant member for implanting in living tissue is provided. The implant is formed of an open structured tantalum filament having a cross-sectional size of less than about 250 microns.

CROSS REFERENCE TO RELATED APPLICATION

This Application is a continuation-in-part (CIP) of my U.S. applicationSer. No. 14/328,567, filed Jul. 10, 2014, now U.S. Pat. No. 9,155,605,the contents of which are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to improvements in filament materials. Theinvention has particular utility in connection with biocompatiblefilament materials for use as scaffolding agents for repair andregeneration of defective bone tissue and as a porous metal coating ofsolid body parts as replacement such as for knee, hip joints as well asfor soft tissue fibers such as nerve, tendons, ligaments, cartilage, andbody organ parts, and will be described in connection with such utility,although other utilities such as for use in electrochemical cells, i.e.batteries, are contemplated.

BACKGROUND ART

There is a substantial body of art describing various materials andtechniques for using biocompatible implants in the human body. Some ofthe more important needs are for hip joints, knee and spinereconstruction and shoulder joints. These implants are usually metallicsince they are load bearing structures and require relatively highstrengths. To insure proper fixation to the bone, a porous metal coatingis applied to the implant surface, and is positioned such that it is incontact to the bone. This is to promote bone growth into and through theporous coating to insure a strong bond between the bone and the metallicimplant. This coating requires a high degree of porosity, typicallygreater than 50% and as high as 70-80% with open connective pore sizesvarying from 100μ to 500μ. These implants must have significantcompression strength to resist loads that these joints can experience.The modulus must also be closely matched to that of the bone to avoidstress degradation of the adjoining tissue.

In addition to the use of tantalum fibers for bone growth, repair andattachment of the implant, it can also be used effectively as a scaffoldfor soft tissue growth and can provide either a permanent or temporarysupport to the damage tissue/organ until functionalities are restored.Regardless of whether it's soft or hard tissue repair/replacement, allbiomaterial will exhibit specific interactions with cells that will leadto stereotyped responses. The ideal choice for any particular materialand morphology will depend on various factors, such are osteoinduction,Osteoconduction, angiogenesis, growth rates of cells and degradationrate of the material in case of temporary scaffolds.

Tissue engineering is a multidisciplinary subject combining theprinciples of engineering, biology and chemistry to restore thefunctionality of damaged tissue/organ through repair or regeneration.The material used in tissue engineering or as a tissue scaffold caneither be naturally derived or synthetic. Further classification can bemade based on the nature of application such as permanent or temporary.A temporary structure is expected to provide the necessary support andassist in cell/tissue growth until the tissue/cell regains originalshape and strength. These types of scaffolds are useful especially incase of young patients where the growth rate of tissues are higher andthe use of an artificial organ to store functionality is not desired.However, in the case of older patients, temporary scaffolds fail to meetthe requirements in most cases. These include poor mechanical strength,mismatch between the growth rate of tissues and the degradation rate ofsaid scaffold. Thus older patients need to have a stronger scaffold,which can either be permanent or have a very low degradation rate. Mostof the work on scaffolding has been done on temporary scaffolds owing tothe immediate advantages realized of the materials used and the ease ofprocessing. Despite early success, tissue engineers have facedchallenges in repairing/replacing tissues that serve predominantlybiomechanical roles in the body. In fact, the properties of thesetissues are critical to their proper function in vivo. In order fortissue engineers to effectively replace these load-bearing structures,they must address a number of significant questions on the interactionsof engineered constructs with mechanical forces both in vivo and invitro.

Once implanted in the body, engineered constructs of cells and matriceswill be subjected to a complex biomechanical environment, consisting oftime-varying changes in stresses, strains, fluid pressure, fluid flowand cellular deformation behavior. It is now well accepted that thesevarious physical factors have the capability to influence the biologicalactivity of normal tissues and therefore may plays an important role inthe success or failure of engineered grafts. In this regard, it isimportant to characterize the diverse array of physical signals thatengineered cells experience in vivo as well as their biological responseto such potential stimuli. This information may provide an insight intothe long-term capabilities of engineered constructs to maintain theproper cellular phenotype.

Significant advances have been made over the last four decades in theuse of artificial bone implants. Various materials ranging frommetallic, ceramic and polymeric materials have been used in artificialimplants especially in the field of orthopedics. Stainless steel(surgical grade) was widely used in orthopedics and dentistryapplications owing to its corrosion resistance. However laterdevelopments included the use of Co—Cr and Ti alloys owing tobiocompatibilities issues and bioinertness. Currently Ti alloys andCo—Cr alloys are the most widely used in joint prostheses and otherbiomedical applications such as dentistry and cardio-vascularapplications. Despite the advantages of materials such as Ti and Co—Crand their alloys in terms of biocompatibility and bio inertness, reportsindicated failure due to wear and wear assisted corrosion. Ceramics wasa good alternative to metallic implants but they too had theirlimitation in their usage. One of the biggest disadvantages of usingmetals and ceramics in implants was the difference in modulus comparedto the natural bone. (The modulus of articular cartilage varies from0.001-0.1 GPa while that of hard bone varies from 7-30 GPa). Typicalmodulus values of most of the ceramic and metallic implants used liesabove 70 GPa. This results in stress shielding effect on bones andtissues which otherwise is useful in keeping the tissue/bone functional.Moreover rejection by the host tissue especially when toxic ions in thealloy, such as Vanadium in Ti alloy, are eluted causes discomfort inpatients necessitating revisional operations to be performed. Polymershave modulus within the range of 0.001-0.1 GPa and have been used inmedicine for applications which range from artificial implants, i.e.,acetabular cup, to drug delivery systems owing to the advantages ofbeing chemically inert, biodegradability and possessing properties,which lies close to the cartilage properties. With the developments inthe use of artificial implants there were growing concerns on thebiocompatibility of the materials used for artificial implants and theimmuno-rejection by the host cells. This led to the research on therepair and regeneration of damaged organs and tissues, which started in1980 with use of autologuous (use of grafts from same species) skingrafts. Thereafter the field of tissue engineering has seen rapiddevelopments from the use of synthetic materials to naturally derivedmaterial that includes use of autografts, allografts and xenografts forrepair or regeneration of tissues.

Surface area and surface terrain or topography is one of the importantfactors governing cell adhesion and proliferation, and there have beenmany studies carried out in recent times to investigate the suitabilityof materials such as spider webs and cover slips, fish scales, plasmaclots, and glass fibers. Silk fibers also have been used extensively insurgical applications such as for sutures and artificial blood vessels.Cell adhesion to materials is mediated by cell-surface receptors,interacting with cell adhesion proteins bound to the material surface.In aiming to promote receptor medicated cell adhesion the surface shouldmimic the extracellular matrix (ECM). ECM proteins, which are known tohave the capacity to regulate such cell behaviors as adhesion,spreading, growth, and migration, have been studied extensively toenhance cell-material interactions for both in vivo and in vitroapplications. However, the effects observed for a given protein havebeen found to vary substantially depending on the nature of theunderlying substrate and the method of immobilization. In biomaterialresearch there is a strong interest in new materials especially formetals, which combine the required mechanical properties with improvedbiocompatibility for bone implants and soft tissue repair andreplacement.

The foregoing discussion of the prior art derives in large part from anarticle by Yarlagadda, et al. entitled Recent Advances and CurrentDevelopments in Tissue Scaffolding, published in Bio-Medical Materialsand Engineering 15(3), pp. 159-177 (2005).

As noted supra, high surface area and surface terrain or topography isone of the important factors governing cell adhesion and proliferation.The greater the relative surface area, i.e., the greater the specificsurface of the material the greater cell adhesion and proliferation.Prior attempts to increase specific surface area of materials used forimplants generally involve making the material used for forming theimplant as small as possible. However, making the material as small aspossible adds significantly to material manufacturing cost, and alsocomplicates handling.

See U.S. Pat. No. 5,030,233 to Ducheyne, who discloses a mesh sheetmaterial for surgical implant formed of metal fibers having a fiberlength of about 2 mm to 50 mm, and having a fiber diameter of about 20to about 200 um. According to the '233 patent if the fiber length ismore than about 50 mm, manufacturing becomes difficult. In particular,for fiber lengths in excess of about 50 mm, sieving the fibers becomesimpractical if not impossible. If the diameter of the fibers is lessthan about 20 microns, it is difficult to maintain the average pore sizeof at least 150 μm needed to assure ingrowth of bony tissue. If thefiber diameter is greater than about 200 μm, the flexibility anddeformability become insufficient.

See also U.S. Pat. No. 4,983,184 to Steinemann which describes the useof metallic fibers, circular in cross-section, and having a thickness of5 to 20 micrometers, formed of titanium alloy, bundled together as 200to 1000, or even up to 3000 fibers, for forming an alloplasticreinforcing material for soft tissue. More particularly, Steinemannteaches titanium and titanium alloys for producing artificial softtissue components and/or for reinforcing natural soft tissue componentscomprising elongate titanium or titanium alloy wires of diameter 5 to 20micron diameter, bundled together for use as an artificial soft tissuecomponent and reinforcement for a soft tissue component in a human oranimal. Pure tantalum metal is known to have excellent bio-compatibleproperties and has for many years been used in the medical field.Indeed, a paper by Bobyn, Stackpool, Hacking, Tanzer and Krygier in theJournal of Bone & Joint Surgery (Br), Vol. 81-B, No. 5, September, 1999,and in U.S. Pat. No. 5,282,861 to Kaplan describes the use of poroustantalum bio material for use to promote bone growth and adhesion of themetallic implants, which material currently is marketed by the ZimmerCorp.

SUMMARY OF THE INVENTION

It is well known that as the diameter of metal filaments are reducedbelow 25 microns, it becomes increasingly difficult to assemble thesemicron sized fiber into a scaffolding structure. The most importantrequirement is the need for the scaffold to maintain a sufficient solidand stable porosity structure during and after implantation into thebody. The present invention provides this characteristic and retains thehigh specific surface area and improved mechanical performance. Inparticular, the invention provides elongate elements havingcross-sectional shapes including elongate paths open on one side. By wayof example, as can be seen in FIG. 1 and FIG. 2, a filament may consistof hollow sections having a Z-shape or flagged-Y-shape, inside a roundfilament constructed with tantalum or other biocompatible valve metalconnectors which are thin, uniform in thickness and continuous innature. However, other shapes are possible as will be described below.To insure lateral stability, the filaments can also be twisted tofurther the resistance to compressive forces. In addition, othergeometric arrangement also can be made in similar fashion.

It is expected that depending on the specific requirement of theimplant, the filament diameter can range from about 25 microns to about250 microns, preferably about 50 microns, with the connector thicknessbetween about 5 to about 50 microns.

In one aspect of the invention there is provided a tissue implant memberfor implanting in living tissue, comprising a mechanically stableflexible filament consisting essentially of thin open structural valvemetal elements of uniform thickness which have a cross-sectional size ofless than 250 microns.

Preferably, the valve metal is a metal selected from the groupconsisting of tantalum, titanium, niobium, hafnium and zirconium andtheir alloys.

In one embodiment the implant comprises a tissue scaffold for supportingtissue growth, preferably selected from the group consisting of bone,nerve cells, tendons, ligaments, cartilage and body organ parts.

The invention also provides a method for promoting tissue growth in abody comprising implanting in the body a tissue implant member as abovedescribed.

In one embodiment the tissue is selected from the group consisting ofbone, nerve cells, tendon, ligaments or cartilage and body organ parts.

The invention also provides a tissue implant member for implanting inliving tissue consisting essentially of a mechanically stable flexiblestructure of open structured tantalum elements in which the tantalumfilaments have a cross-sectional size of less than 250 microns.

Preferably, the structural tantalum elements inside the filament have across-sectional thickness of from about 5 to less than about 50 microns,more preferably from about 2 to less than about 30 microns.

In one embodiment the implant comprises a tissue scaffold for supportingtissue growth.

Preferably, the tissue is selected from the group consisting of bone,nerve cells, tendon, ligaments, cartilage and body organ parts.

The present invention also provides a method for promoting tissue growthin a body comprising implanting in the body a tissue implant member asabove described.

Preferably, the tissue is selected from the group consisting of bone,nerve cells, tendon, ligaments, cartilage and body organ parts.

BRIEF DESCRIPTION OF THE DRAWINGS

Further features and advantages of the present invention will be seenfrom the following detailed description taken in conjunction with theaccompanying drawings, wherein:

FIGS. 1 and 2 illustrate starting members in accordance with the presentinvention;

FIG. 3 is a schematic block diagram of a process for forming implanttissue members in accordance with the present invention;

FIG. 4 is a member formed in accordance with the present invention;

FIG. 5 is a simplified side elevational view showing casting of a memberin accordance with the present invention; and

FIGS. 6A-6D illustrates cross-sectional views of other members inaccordance with the present invention.

DETAILED DESCRIPTION

As used herein, the term biocompatible valve metal includes tantalum,which is the preferred metal, as well as titanium, niobium, hafnium andzirconium and their alloys. The term “formed essentially of tantalum orother biocompatible valve metal” or “consisting essentially of tantalumor other biocompatible valve metal” means that the filaments comprise atleast 99.0 percent by wt. tantalum or other biocompatible valve metal.

“Open structure” means shaped filaments having a cross-sectional shapeincluding integral connectors.

Referring to FIGS. 1-5, the process starts with the fabrication of valvemetal filaments, such as tantalum, by combining shaped elements 8 oftantalum (see FIGS. 1 and 2) with a ductile material, such as copper toform a billet at step 10. The shaped elements of tantalum are formedfrom thin sheets of tantalum typically between 0.25 mm to 0.50 mm thick.The elements are structured such that they preform as a round filament.Between the tantalum elements, copper is placed and is removed after thebillet is extruded and drawn to the desired final size following theteachings of my prior PCT application nos. PCT/US07/79249 andPCT/US97/23260, and U.S. Pat. Nos. 7,146,709 and 7,480,978.

The billet is then sealed in an extrusion can in step 12, and extrudedand drawn in step 14 following the teachings of my prior PCTapplications Nos. PCT/US07/79249 and PCT/US08/86460, or my prior U.S.Pat. Nos. 7,480,978 and 7,146,709. In one example, the extruded anddrawn filaments are cut or chopped into short segments, typically0.15875 to 0.63500 cm inch long at a chopping station 16. Preferably thecut filaments all have approximately the same length. Actually, the moreuniform the filaments in size, the better. The chopped filaments arethen passed to an etching station 18 where the ductile metal is leachedaway using a suitable acid. For example, where copper is the ductilemetal, the etchant may comprise nitric acid.

Etching in acid removes the copper from between the tantalum filaments.After etching, one is left with a plurality of short filaments oftantalum 15, as shown in FIG. 4. The tantalum filaments are then washedin water, and the wash water is partially decanted to leave a slurry oftantalum filaments in water. The slurry of tantalum filaments in wateris uniformly mixed and is then cast as a thin sheet using, for example,in FIG. 5 “Doctor Blade” casting station 22. Excess water is removed,for example, by rolling at a rolling station 24. The resulting mat isthen further compressed and dried at a drying station 26.

It was found that an aqueous slurry of chopped filaments will adheretogether and was mechanically stable such that the fibers easily couldbe cast into a fibrous sheet, pressed and dried into a stable mat.

The resulting fibrous structure is flexible and has sufficient integrityso that it can be assembled and shaped into an elongate scaffoldingwhere it can then be used. The fibrous structure product made accordingto the present invention forms a porous surface of fibers capable ofmaintaining minimum spacings between fibers with large surfacearea-to-volume, which encourages healthy ingrowth of bone or softtissue.

Various changes may be made in the above without departing from thespirit and scope thereof. More particularly, other shaped fibers havingelongate open pads may be formed. By way of example, as shown in FIG.6A, the fibers may have a X-shape, in cross-section, or a W-shape incross-section as illustrated in FIG. 6B, a starburst shape as shown inFIG. 6C, a U-shape as shown in FIG. 6D, which I have given as exemplary.The point is the elongate elements may have a variety of cross-sectionalshapes that form structurally elongate paths open on one side.

The resulting fibrous structure made in accordance with the presentinvention has significant advantages over prior art structures formedfrom solid round filaments. The open structure of the filaments addssignificantly to filament surface area which, as noted supra, addsadvantages in terms of cell adhesion and proliferation. Moreover, thesefilaments can maintain a parallel path—rigid in one direction, to allowtissue to grow on a flat plane driven surface. Conventional smalldiameter solid round filaments adhere in tight bundles, especially whenwet, essentially parallel to one another due to surface tension forces,and causes problems in maintaining an open porosity. By changingfilament structural geometry, we can avoid this problem and maintainseparation of each and every filament and still provide high specificsurface area.

Numerous other arrangements by carding the fibers, meshes, braids andother type arrangements can also be constructed.

Moreover, while the invention has been described in particular for usein connection with biocompatible filament materials for use asscaffolding agents for repair and regeneration of body parts such asbone tissue, nerve, tendons, etc., the elongate filaments havingelongate pads open on one side also advantageously may be used inapplications where high surface area filaments are desired such as, forexample, for use in forming anodes for electrochemical cells, i.e.batteries and/or semi-solid electrodes for use in high densityelectrochemical cells such as lithium batteries.

The invention claimed is:
 1. A tissue implant member for implanting inliving tissue, comprising a mechanically stable structure consistingessentially of thin, elongate elements, each having a long axis, formedof a valve metal, each of said elements having at least one structurallyfixed channel forming an elongate pathway extending from a surface ofsaid element parallel to the element long axis, said at least onechannel being open on at least one side, each of said elements having across-sectional size of less than 250 microns.
 2. The implant as claimedin claim 1, wherein said valve metal elements have a cross-sectionalsize of less than about 50 microns.
 3. The implant as claimed in claim1, wherein the valve metal is a metal selected from the group consistingof tantalum, titanium, niobium, hafnium and zirconium and their alloys.4. The implant of claim 1, wherein the implant comprises a tissuescaffold for supporting tissue growth.
 5. A method for promoting tissuegrowth in a body comprising implanting in the body a tissue implantmember as claimed in claim
 1. 6. The method of claim 5 wherein thetissue is selected from the group consisting of bone, nerve cells,tendon, ligaments or cartilage and body organ parts.
 7. A tissue implantmember for implanting in living tissue consisting essentially of thin,elongate open shape elements, each having a long axis, formed oftantalum, each of said elements having at least one structurally fixedchannel forming an elongate pathway extending from a surface of saidelement parallel to the element long axis, said at least one channelbeing open on one side, each of said elements having a cross-sectionalsize of less than 250 microns.
 8. The implant as in claim 7, whereinsaid structural tantalum elements have a cross-sectional size of fromabout 5 to less than about 50 microns.
 9. The implant of claim 8,wherein the implant comprises a tissue scaffold for supporting tissuegrowth.
 10. The implant as in claim 7, wherein said structural tantalumelements have a cross-sectional size of from about 2 to less than about50 microns.
 11. The implant as in claim 10, wherein the implantcomprises a tissue scaffold for supporting tissue growth.
 12. A methodfor promoting tissue growth in a body comprising implanting in the bodya tissue implant member as claimed in claim
 7. 13. The method of claim12, wherein the tissue is selected from the group consisting of bone,nerve cells, tendon, ligaments, cartilage and body organ parts.
 14. Anelongate filament comprising a mechanically stable structure consistingessentially of thin, elongate elements, each having a long axis, formedof a valve metal, each of said elements having at least one structurallyfixed channel forming an elongate pathway extending from a surface ofsaid element parallel to the element long axis, said at least onechannel being open on one side, each of said elements having across-sectional size of less than 250 microns.
 15. The filament asclaimed in claim 14, wherein said valve metal elements have across-sectional size of less than about 50 microns.
 16. The filament asclaimed in claim 14, wherein the valve metal is a metal selected fromthe group consisting of tantalum, titanium, niobium, hafnium andzirconium and their alloys.